The development and use of modified nucleotides has expanded the range of nucleic acid analysis techniques. For example, the modified non-natural nucleotides of Eragen Corporation expand the alphabet of bases that may be used in nucleic acid technologies (See e.g., U.S. Pat. Nos. 5,216,141, 5,432,272, 5,958,702, 5,965,364, 6,001,983, 6,037,120, and 6,140,496 and patent application Ser. Nos. 09/415,966, 09/538,338, 09/993,757, 60/205,712, 60/240,398, 60/282,831, 60/240,397, 60/252,783, and 60/253,382, each of which is incorporated herein in its entirety). While these modified nucleotides have been found useful, compositions and methods that provide improved sensitivity and flexibility in using such products in nucleic acid analysis methods are needed.
Modified nucleotides also find use in nucleic acid amplification reactions such as the polymerase chain reaction. See, e.g., U.S. Ser. No. 09/861,292, published as Publication No. 2002/0150900, and U.S. Ser. No. 10/977,615, published as Publication No. 2004/0106108, each of which is incorporated herein by reference in its entirety. While these applications have been found useful, methods and compositions that reduce background signal and improve assay sensitivity are needed.